DE10052590A1 - Use of 2-hydrazino-1,3-thiazoles as antioxidants - Google Patents

Abstract

The invention relates to 2-hydrazino-1,3-thiazoles or the salts thereof which can be used as active ingredients in cosmetic and dermatological preparations and preparations used for nourishment or culinary purposes in order to protect cells and the tissue of mammals, said preparations protecting against the harmful influence of reactive oxygen species and free radicals.

Description

The invention relates to the use of 2-hydrazino-1,3-thiazoles as antioxi dantien or radical scavengers, preferably as antioxidants or radical scavengers in cosmetic, dermatological as well as serving nutrition or pleasure Preparations. The invention also relates to the use of these preparations to protect mammalian cells and tissues from accelerating aging harmful effects of radicals and reactive oxygen compounds fertilize.

A number of diseases and age damage to organisms, especially of Mammals are characterized by reactive oxygen species and other reactive radicals solved or reinforced. So z. B. special aspects of photo-aging of the skin, damage to the retina in age-related macular degeneration, the Trü Exercise of the lens in cataracts, special types of cancerogenesis and the arterio sclerosis causally related to the reaction biologically more important Molecules such as deoxyribonucleic acid or proteins with free Seen radicals.

For cosmetic, dermatological as well as serving nutrition or pleasure Preparations are searched for active ingredients, in particular in physiological systems especially in mammals, the natural defense mechanisms against free radicals and support reactive oxygen compounds or as protective substances in Kos Metics, pharmaceuticals or foods whose oxidation sensitive Protect components from autoxidation.

Antioxidants are substances that are in comparison to the oxidizable substrate small concentrations significantly delay the oxidation or completely ver prevent. Many antioxidants act as radical scavengers and / or at the same time Complexing agent for heavy metal ions.  

It was found that 2-hydrazino-1,3-thiazoles of the general formula

or their salts,
in which
X represents a nitrogen atom or a substituted carbon atom CQ ² ,
and
either
Q ¹ and Q ² independently of one another are hydrogen atoms,
optionally hydroxyl- or alkyloxy-substituted unbranched, ver branched or cyclic alkyl, alkenyl, 1-oxoalkyl or 1-oxoalkenyl groups with 1 to 18 carbon atoms,
optionally substituted aryl groups with 6 to 15 carbon atoms,
optionally substituted heterocyclyl groups with 2 to 15 carbon atoms and at least one heteroatom selected from the group consisting of oxygen, nitrogen or sulfur,
optionally substituted arylalkyl or aryl-1-oxoalkyl groups of 7 to 16 carbon atoms,
Halogen atoms, nitro groups or
Represent groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ NR ⁴ R ⁵ or -PO (OR ⁴ ) (OR ⁵ ),
or
Q ¹ and Q ² together represent a radical of the general formula (II)

represent
in which
X ¹ , X ² and X ³ independently of one another represent either nitrogen atoms or carbon atoms with the radicals R ¹ , R ² or R ³ ,
and
R ¹ , R ² and R ³ independently of one another are hydrogen atoms,
optionally hydroxyl- or alkyloxy-substituted unbranched, ver branched or cyclic alkyl, alkenyl, 1-oxoalkyl or 1-oxoalkenyl groups with 1 to 18 carbon atoms,
optionally substituted aryl groups with 6 to 15 carbon atoms,
optionally substituted heterocyclyl groups with 2 to 15 carbon atoms and at least one heteroatom selected from the group consisting of oxygen, nitrogen or sulfur,
optionally substituted arylalkyl or aryl-1-oxoalkyl groups of 7 to 16 carbon atoms,
Halogen atoms, nitro groups or
Represent groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ NR ⁴ R ⁵ or -PO (OR ⁴ ) (OR ⁵ )
and
R ⁴ and R ⁵ independently of one another are hydrogen atoms, optionally hydroxyl- or alkyloxy-substituted unbranched, branched or cyclic alkyl, alkenyl, 1-oxoalkyl or 1-oxoalkenyl groups with 1 to 18 carbon atoms, optionally substituted aryl groups with 6 to 15 carbon atoms, optionally substituted arylalkyl or aryl-1-oxoalkyl groups of 7 to 16 carbon atoms,
represent
can be used as antioxidants or radical scavengers.

The 2-hydrazino-1,3-heteroazoles according to the invention can also be in the form of their Tautomers are present.

An unbranched, branched or cyclic alkyl group can be 1 to 18, preferred Contain 1 to 8, particularly preferably 1 to 6 carbon atoms. For example may be mentioned: methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, tert-butyl, 2- Methyl, 2-methylprop-1-yl, cyclopropyl, cyclopropylmethyl, 2,2-dimethylcyclo propyl, cyclobutyl, cyclopentyl, cyclohexyl and various positional isomers of Methylpentyl.

A straight, branched or cyclic alkenyl group can be 2 to 18 before contains 2 to 8, particularly preferably 2 to 6, carbon atoms. example Wise may be mentioned: ethenyl, 1- or 2-propenyl, 1-, 2- or 3-butenyl, 2-methyl-1- propenyl, 2-methyl-2-propenyl, 1,3-butadienyl, 1,3-pentadienyl, 1,4-pentenyl, 2,4- Pentenyl, the various different straight-chain, cyclic or branched Isomers of the pentenyl, hexenyl radical. Ethenyl, 1- or are particularly preferred 2-propenyl, 1-, 2- or 3-butenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, 3- Methyl-1-pentenyl, 3-methyl-2-pentenyl, 3-methyl-3-pentenyl, cyclopentenyl, Cyclopentadienyl, cyclohexadienyl and cyclohexenyl.  

An unbranched, branched or cyclic 1-oxo-alkyl group can be 1 to 18, preferably contain 1 to 8, particularly preferably 1 to 5 carbon atoms. at Examples include: formyl, acetyl, propionyl, 2-methylpropionyl, butanoyl, 2-methylbutanoyl, 3-methylbutanoyl, 2,2-dimethylpropionyl, cyclopropylcarboxyl.

An unbranched, branched or cyclic 1-oxo-alkenyl group can contain 3 to 18, preferably contain 3 to 8, particularly preferably 3 to 5 carbon atoms. at Examples include: prop-2-enoyl, 2-methylprop-2-enoyl, 2-ethyl-prop-2- enoyl, E- or Z-2-butenoyl, 3-butenoyl, E- or Z-2-methylbut-2-enoyl, E- or Z-3-methylbut-2-enoyl, Z- or E- 2-pentenoyl, Z- or E- 3-pentenoyl.

Aryl groups with 6 to 15 carbon atoms, preferably 6 to 10 carbon atoms can be, for example: phenyl and naphthyl.

A heterocyclyl group with 2 to 15 carbon atoms and at least one An atom from the group consisting of oxygen, sulfur or nitrogen in the ring generally exists mean from 1 to 3, preferably 1 or 2 five or six-membered rings. The Heterocyclyl group preferably contains 1 to 4, particularly preferably 1 or 2 Hetero atoms. Furan, pyrrole, thiophene, indole, isoindole, benzofuran, Isobenzofuran, benzothiophene, isobenzothiophene, pyrazole, imidazole, 1,3- or 1,2- Oxazole, 1,3- or 1,2-thiazole, 1,3- or 1,2-benzimidazole, 1,3- or 1,2-benzoxazole, 1,3- or 1,2-benzothiazole, pyridine, pyrimidine, pyrazine, 1,2-, 1,3- or 1,4-oxazine, 1,2-, 1,3- or 1,4-thiazine, quinoline, isoquinoline, benzo-1,2-, -1,3- or -1,4-diazine or their partially or fully saturated derivatives, e.g. B. tetrahydrofuran, 1,3- Dioxolane, pyrrolidine, pyrroline, 1,3- or 1,4-dioxane, piperidine, tetrahydro-2H-py ran, piperazine, oxirane or aziridine. Furan, pyrrole, In are particularly preferred dol, imidazole, 1,3-thiazole, 1,3-benzothiazole, pyridine, pyrimidine, quinoline, Isoquinoline or its partially or fully saturated derivatives, e.g. B. Tetrahydro furan, 1,3-dioxolane, pyrrolidine, 1,3- or 1,4-dioxane, piperidine or tetrahydro-2H- pyran.  

An arylalkyl group can consist of 6 to 1 S carbon atoms, preferably 7 to 8 Carbon atoms exist and can be, for example: benzyl, 2- or 1-phenyl ethyl.

An aryl-1-oxo-alkyl group can have 6 to 15 carbon atoms, preferably 7 up to 8 carbon atoms and can be, for example: benzoyl, phenyl acetyl.

Substituents of the aryl, arylalkyl, aryl-1-oxoalkyl and heterocyclyl groups can Examples include: hydrogen atoms, alkyl, hydroxy, alkyloxy, thio, Al kylthio, amino, alkylamino, dialkylamino, nitro, iodine, bromine, fluorine, chlorine, Azido, thiocyanato, isothiocyanato, cyanato, isocyanato, nitrile, isonitrile, Phosphate, alkyl phosphate, dialkyl phosphate, sulfonic acid, alkyl sulfonate, sulfone amide, dialkylsulfonamide or alkylsulfonamide residues. Are particularly preferred Hydrogen atoms, alkyl, hydroxy, alkyloxy, amino, dialkylamino, bromine, Fluorine, chlorine, nitrile, sulfonic acid, sulfonamide or alkyl sulfonate residues.

Preference is given to using the 2-hydrazino-1,3-thiazoles of the general formula (I)

or their salts,
in which
X represents a nitrogen atom or a carbon atom CQ ² substituted by Q ² ,
and
either
Q ¹ and Q ² independently of one another are hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl or acetyl groups, chlorine or fluorine atoms, nitro groups, groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ NR ⁴ R ⁵ , -PO (OR ⁴ ) (OR ⁵ ), or on the aromatic optionally with alkyl, hydroxy, Alkyloxy, amino, dialkylamino, bromine, fluorine, chlorine, nitrile, sulfonic acid, sulfonamide or alkylsulfonate radicals represent substituted phenyl, pyridyl, pyrazinyl, phenylmethyl or benzoyl groups,
or
Q ¹ and Q ² together represent a radical of the general formula (II)

represent
in which
X ¹ , X ² and X ^{3 represent} carbon atoms with the radicals R, R ² and R ³ ,
and
R ¹ , R ² and R ³ independently of one another are hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl or acetyl groups, phenyl, pyridyl , Pyrazinyl groups, phenylmethyl, 4-methylphenylmethyl, 4-methoxyphenylmethyl or benzoyl groups, chlorine or fluorine atoms, nitro groups, groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ NR ⁴ R ⁵ or -PO (OR ⁴ ) (OR ⁵ )
and
R ⁴ and R ⁵ independently of one another are hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl, acetyl, propionyl or pivaloyl groups, phenyl, Pyridyl, pyrazinyl, phenylmethyl, 4-methylphenylmethyl, 4-methoxyphenylmethyl or benzoyl groups
as antioxidants or radical scavengers.

The use of is particularly preferred
2-hydrazino-1,3-benzothiazole
5,6-dimethoxy-2-hydrazino-1,3-benzothiazole
6-Methoxy-2-hydrazino-1,3-benzothiazole
2-hydrazino-1,3-benzothiazole-5-sulfonic acid
2-hydrazino-1,3-benzothiazole-6-sulfonic acid
6-tert-butyl-2-hydrazino-1,3-benzothiazole
6-methyl-2-hydrazino-1,3-benzothiazole
2-hydrazino-thiazolo [5,4-b] pyridine
2-hydrazino-1,3-benzoxazol
2-hydrazino-1H-benzimidazole
2-hydrazino-5- (4-fluorophenyl) -1,3,4-thiadiazole
2-hydrazino-4-phenyl-1,3-thiazole
2-hydrazino-4-methyl-1,3-thiazole hydrochloride
as antioxidants or radical scavengers.

Surprisingly, it has now been found that the 2-hydra according to the invention zino-1,3-thiazoles are very good radical scavengers and strong antioxidants. Prefers they are suitable as radical scavengers. In particular, the 2- Hydrazino-1,3-thiazoles are able to counter the harmful effects of free radicals and / or oxidative processes, for example induced by UV light be suppressed on and / or in human skin and the natural to support antioxidant processes. Therefore, they can be used as active ingredients in kosme tables or dermatological skin lightening agents can be used. The 2-hydrazino-1,3-thiazoles according to the invention are also very good Antoxi dantien for highly unsaturated lipids such as squalene, lycopene, carotenes, Docosahexaenoic acid, eicosapentaenoic acid, α- or γ-linolenic acid or linoleic acid as well as for fatty oils containing (poly) unsaturated fatty acids, such as Soybean oil, linseed oil, safflower oil, borage seed oil, evening primrose oil, fish oil, or olive oil Sunflower oil. Therefore, they can serve in the diet or enjoyment the preparations containing such lipids are used as antioxidants become. In particular, the 2-hydrazino-1,3-thiazoles according to the invention are also suitable for Stabilization of the pure lipids or fatty oils or mixtures thereof outstandingly suitable.

The 2-hydrazino-1,3-thiazoles according to the invention can preferably in pharma ceutical, cosmetic or dermatological preparations, preferably for protection of cells and tissues of mammals, especially human skin, as well in foods against the harmful effects of free radicals and reactive oxygen species can be used. Of course, the inventions 2-hydrazino-1,3-thiazoles according to the invention and / or the preparations containing the 2-Hydrazino-1,3-thiazoles according to the invention, also analogously in other Einsatzge offer to be used.

The compounds therefore also relate to cosmetic, dermatological and nutritional or pleasure-making preparations containing the 2-hydrazino-1,3-thiazoles of the general formula (I)

or their salts,
in which
X represents a nitrogen atom or a substituted carbon atom CQ ² ,
and
either
Q ¹ and Q ² independently of one another are hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl or acetyl groups, chlorine or fluorine atoms, nitro groups, groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ NR ⁴ R ⁵ , -PO (OR ⁴ ) (OR ⁵ ), or on the aromatic optionally with alkyl, hydroxy, Alkyloxy, amino, dialkylamino, bromine, fluorine, chlorine, nitrile, sulfonic acid, sulfonamide or alkylsulfonate radicals represent substituted phenyl, pyridyl, pyrazinyl groups, phenylmethyl or benzoyl groups,
or
Q ¹ and Q ² together represent a radical of the general formula (II)

represent
in which
X ¹ , X ² and X ^{3 represent} carbon atoms with the radicals R ¹ , R ² and R ³ ,
and
R ¹ , R ² and R ³ independently of one another are hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl or acetyl groups, phenyl, pyridyl , Pyrazinyl groups, phenylmethyl, 4-methylphenylmethyl, 4-methoxyphenylmethyl or benzoyl groups, chlorine or fluorine atoms, nitro groups, groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ NR ⁴ R ⁵ or -PO (OR ⁴ ) (OR ⁵ )
and
R ⁴ and R ⁵ independently of one another are hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl, acetyl, propionyl or pivaloyl groups, phenyl, Pyridyl, pyrazinyl, phenylmethyl, 4-methylphenylmethyl, 4-methoxyphenylmethyl or benzoyl groups.

The cosmetic, dermatological and nutrition or Preparations for enjoyment support the in physiological systems natural defense mechanisms against free radicals and reactive oxygen bonds and protect in cosmetics, pharmaceuticals, food or beverages means their components sensitive to oxidation before autoxidation or photooxi dation.

The partially known 2-hydrazino-1,3-thiazoles can, for example, according to the in Organic Preparations and Procedures Int. 1974, 6 (4), 179-182  Process can be prepared from the 2-amino-1,3-thiazoles. The latter can for example from the corresponding anilines or heterocyclic amines by reaction with inorganic thiocyanate salts and subsequent oxidative ring closure of the N-arylthiourea are shown (J. Indian Chem. Soc. 1989, 66, 39-41).

The 2-hydrazino-1,3-benzothiazoles according to the invention can, for example, from starting from an optionally substituted aniline by reaction with potassium, Sodium or ammonium thiocyanate, then by chlorine, bromine or iodine average oxidative ring closure and finally by reaction with hydrazine or hydrazine hydrate.

The preparation can be illustrated using the exemplary example 2-hydrazino-6-tert-butyl-1,3-benzothiazole by the following formula:

The preparations according to the invention, containing the 2-hydrazino-1,3-thiazoles, are produced using conventional methods known per se, in such a way that one or more of the 2-hydrazino-1,3-heteroazoles according to the invention of the general Formula I or its salts are incorporated into the formulations which like are commonly composed and for treatment, protection, care and the Cleaning the skin or hair, as make-up products and as food or Luxury goods can serve.  

The preparations according to the invention contain 2-hydrazino-1,3-thiazoles in one effective amount and possibly other ingredients. They contain 0.0001% by weight up to 30% by weight, preferably 0.001 to 20% by weight, but in particular 0.001% by weight up to 5% by weight, based on the total weight of the formulation, of the 2-hydrazino-1,3-thiazoles according to the invention and can be "water in Oil "-," Oil in Water "-," Water in Oil in Water "- or" Oil in Water in Oil "- Emulsions, as microemulsions, as gels, as solutions for. B. in oils, alcohols or silicone oils. Other usual auxiliaries and additives can be found in Amounts from 5 to 99.9999% by weight, preferably 10 to 80% by weight, based on the total weight of the formulation. Furthermore, the Formulations water in an amount up to 99.999 wt .-%, preferably 5 to 80% by weight, based on the total weight of the formulation.

To prepare the preparations according to the invention, in a further Embodiment also the 2-hydrazino-1,3-thiazoles of the general formula I. previously in liposomes, e.g. B. starting from phosphatidylcholine, in microspheres, in Nanospheres or in capsules made of a suitable matrix, e.g. B. from natural or synthetic waxes, for example beeswax, carnauba wax, silicone wax or stearyl alcohol, eicosanol, cetyl alcohol, stearin or paraffin wax or made of gelatin. Another embodiment exists in that the 2-hydrazino-1,3-thiazoles of the general formula I previously with Complexing agents, for example with cyclodextrins or cyclodextrin derivatives, preferably methylcyclodextrin, can be complexed.

The cosmetic and dermatological preparations according to the invention can contain cosmetic auxiliaries and additives, as is usually the case in such Preparations are used, e.g. B. sunscreen (e.g. organic or inorganic light filter substances, preferably micropigments), preservatives medium, bactericides, fungicides, virucides, cooling agents, plant extracts, inflammable anti-aging agents, substances that accelerate wound healing (e.g. chitin or chitosan and its derivatives), film-forming substances (e.g. polyvinylpyrrolidones  or chitosan or its derivatives), common antioxidants, Vitamins (e.g. vitamin C and derivatives, tocopherols and derivatives, vitamin A and Derivatives), 2-hydroxycarboxylic acids (e.g. citric acid, malic acid, L-, D-, or d1- Lactic acid), skin lightening agents (e.g. kojic acid, hydroquinone or arbutin), Skin colorants (e.g. walnut extracts or dihydroxyacetone), perfumes, sub die cut to prevent foaming, dyes, pigments, a coloring Have an effect, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances (e.g. glycerin or urea), fats, oils, unsaturated fatty acids or their derivatives (e.g. Linol acid, α-linolenic acid, γ-linolenic acid or arachidonic acid and their respective natural or synthetic esters), waxes or other common components of a cosmetic or dermatological formulation such as alcohols, polyols, poly mers, foam stabilizers, electrolytes, organic solvents, silicone derivatives or chelating agents (e.g. ethylenediaminetetraacetic acid and derivatives).

The amounts of cosmetic or dermatological amounts to be used in each case auxiliaries and additives and perfume can depend on the type of each product is easily determined by a specialist simply by trying it out become.

The cosmetic or dermatolo according to the invention are used Mixtures containing 2-hydrazino-1,3-thiazoles of the general Formula I, in the usual way for cosmetics on the skin and / or hair in sufficient amount applied.

The cosmetic or dermatological according to the invention can preferably Preparations containing 2-hydrazino-1,3-thiazoles of the general formula I or their salts, also contain active ingredients for skin lightening. In particular can the topical cosmetic compositions according to the invention also benzaldoximes with min at least one aromatic hydroxy or alkoxy group, kojic acid, kojic acid derivatives, ascorbic acid, ascorbic acid derivatives, hydroquinone, hydroquinone derivatives,  sulfur-containing molecules (e.g. glutathione or cysteine) or other synthe contain tables or natural active ingredients for skin lightening, the latter also in the form of an extract from plants (e.g. tocopherols and derivatives, arbutin (e.g. from Bearberry extract), Aloesin (e.g. from Aloe extract), Grapefruit extract and Rice extract) can be used.

The amount of the aforementioned exemplary active ingredients for skin lightening (a or more compounds) can be used in the cosmetic or dermatological preparations 0.001 to 30% by weight, preferably 0.001 to 20% by weight, particularly preferably 0.001 to 5% by weight, based on the total weight the preparation.

Such cosmetic or dermatological accessories are particularly preferred riding that is also in the form of a sunscreen. This ent hold in addition to an effective portion of the 2-hydrazino-1,3-thiazoles of the general Formula I also sunscreen substances, preferably organic or inorganic Light filter substances, in particular micropigments. The skin according to the invention Whitening agents can also entail UVA and / or UVB filter substances hold, the total amount of filter substances 0.1 to 30 wt .-%, preferably 0.5 to 10% by weight, based on the total weight of the preparations, can be, whereby one obtains sunscreens for skin and hair. As UV Filter substances can, for example, 3-benzylidene camphor derivatives (e.g. 3- (4- Methylbenzylidene) -d1-camphor), aminobenzoic acid derivatives (e.g. 4- (N, N-Di methylamino) 2-ethylhexyl benzoate or menthyl anthranilate), 4-methoxy cinnamates (e.g. 2-ethylhexyl p-methoxycinnamate or isoamyl p-methoxycinna mat), benzophenones (e.g. 2-hydroxy-4-methoxybenzophenone), one or more times sulfonated UV filters [e.g. B. 2-phenylbenzimidazole-5-sulfonic acid, Sulisobenzone or 1,4-bis (benzimidazolyl) benzene-4,4 ', 6,6'-tetrasulfonic acid or 3,3' - (1,4-Phe nylendimethyliden) bis (7,7-dimethyl-2-oxo-bicyclo [2,2,1] heptane-1-methanesulfonic acid) and their salts], salicylates (e.g. 2-ethylhexyl salicylate or homomenthyl salicylate), triazines {e.g. B. 2,4-bis- [4- (2-ethylhexyloxy) -2-hydroxyphenyl] -6- (4-  methoxyphenyl) -1,3,5-triazine, 4,4 '- ([6 - ([(1,1-dimethylethyl) aminocarbonyl] - phenylamino) -1,3,5-triazine-2,4-diyl] diimino) bisbenzoesäurebis- (2-ethylhexyl) - ester)}, 2-cyanopropenoic acid derivatives (e.g. 2-ethylhexyl-2-cyano-3,3-diphenyl-2- propenoate), dibenzoyl derivatives (e.g. 4-tert-butyl-4'-methoxydibenzoylmethane), polymer-bound UV filters (e.g. polymer of N- [2- (or. 4) - (2-oxo-3- bornylidene) methyl] benzylacrylamide) or pigments (e.g. titanium dioxide, zirconium di oxides, iron oxides, silicon oxides, manganese oxides, aluminum oxides, cerium oxides or Zinc oxides) can be used.

In a further preferred embodiment of the invention, in addition to the 2-hydrazino-1,3-thiazoles according to the invention, the preparations according to the invention also contain other antioxidants or free radical scavengers. In particular, all antioxidants suitable or customary for the applications according to the invention can be used as other antioxidants. The antioxidants are advantageously selected from the group consisting of amino acids (e.g. glycine, histidine, 3,4-dihydroxyphenylalanine, tyrosine, tryptophan) and their derivatives, imidazoles (e.g. urocanic acid) and their derivatives, peptides (D, L-carnosine, D-carnosine, L-carnosine, anserine) and their derivatives, carotenoids, carotenes (e.g. α-carotene, β-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and its derivatives, Aurothioglucose, propylthiouracil and other thiols (e.g. thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl and N-acyl derivatives or their alkyl esters) as well as their salts, dilaurylthiodipropionate, distearylthiodipropionate, thiodipropolic acid and their amidophenol phenolic acid and their derivatives B. Homovanillic acid, 3,4-dihydroxyphenylacetic acid, ferulic acid, sinapic acid, caffeic acid, dihydroferulic acid, dihydrocaffeic acid, vanillomandelic acid or 3,4-dihydroxymandelic acid ami de of 3,4-dihydroxybenzyl-, 2,3,4-trihydroxy benzyl- or 3,4,5-trihydroxybenzylamine), further (metal) chelators (e.g. B. 2-hydroxy fatty acids, phytic acid, lactoferrin), humic acid, bile acids, bile extracts, bilirubin, biliverdin, folic acid and its derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and its derivatives (e.g. ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate) , Tocopherols and derivatives (e.g. vitamin E acetate), vitamin A and derivatives (e.g. vitamin A palmitate), rutinic acid and its derivatives, flavonoids (e.g. quercetin, α-glucosylrutin) and their derivatives, phenolic acids (e.g. gallic acid, ferulic acid) and their derivatives (e.g. propyl gallate, ethyl ester, octyl ester), furfurylidene glucitol, dibutyl hydroxytoluene, butylated hydroxyanisole, uric acid and its derivatives, mannose and their derivatives, zinc and its derivatives (e.g. ZnO, ZnSO ₄ ), selenium and its derivatives (e.g. selenomethionine), stilbenes and their derivatives (e.g. stilbene oxide, resveratrol) and the derivatives of these active substances which are suitable according to the invention.

The amount of the aforementioned other antioxidants (one or more compounds dungen), which are not identical to the 2-hydrazino-1,3-thiazoles according to the invention are in the preparations according to the invention is preferably 0.0001 to 30% by weight, particularly preferably 0.01 to 10% by weight, particularly preferably 0.01 up to 5% by weight, based on the total weight of the preparations.

In addition to the 2-hydrazino-1,3-thiazoles according to the invention can of course several other antioxidants are used.

The lipid phase in the cosmetic or dermatological invention Preparations containing 2-hydrazino-1,3-thiazoles of the general formula I or their salts can advantageously be selected from the following groups of substances: Mineral oils (advantageous paraffin oil), mineral waxes, hydrocarbons (advantageous Squalane or squalene), synthetic or semi-synthetic triglyceride oils (e.g. Triglycerides of capric or caprylic acid), natural oils (e.g. castor oil, olives oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil, borage seed oil and the like), natural ester oils (e.g. jojoba oil), synthetic ester oils (preferably esters of saturated and / or unsaturated, linear and / or branched alkane carboxylic acids of 3 to 30 carbon atoms with ge saturated and / or unsaturated, linear and / or branched alcohols with 3 to  30 carbon atoms and esters of aromatic carboxylic acids with saturated and / or unsaturated, linear and / or branched alcohols with 3 to 30 C atoms, especially selected from the group of isopropyl myristate, isopropyl stearate, iso propyl palmitate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl laurate, iso octyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethyl hexyl laurate, 2-hexyldecyl stearate, 2-octyldecyl palmitate, oleyl oleate, olerlerucate, Erucyl oleate, erucylerucate and synthetic or natural mixtures thereof Esters), fats, waxes and other natural and synthetic fat bodies preferably esters of fatty alcohols with alcohols with a low C number (e.g. with Isopropanol, propylene glycol or glycerin) or esters of fatty alcohols Low carbon number alkanoic acids or with fatty acids, alkyl benzoates (e.g. mixtures of n-dodecyl, n-tridecyl, n-tetradecyl and n-pentadecyl benzoate) and cyclic or linear silicone oils (such as dimethylpolysiloxanes, diethylpoly siloxanes, diphenylpolysiloxanes and mixed forms thereof).

The aqueous phase of the cosmetic or dermatological invention Preparations containing 2-hydrazino-1,3-thiazoles of the general formula I or their salts, optionally advantageously contains alcohols, diols or polyols low C number, and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerin, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, Propylene glycol monomethyl ether, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analog products, also alcohols low C number, e.g. As ethanol, isopropanol, 1,2-propanediol, glycerin and ins special one or more thickeners, which or which advantageous can be selected from the group silicon dioxide, aluminum silicates, Polysaccharides or their derivatives, e.g. B. hyaluronic acid, xanthan gum, hydroxy propylmethyl cellulose, particularly advantageously from the group of polyacrylates, preferably a polyacrylate from the group of the so-called carbopoles, in each case individually or in combination or from the group of polyurethanes.  

The use of the preparations according to the invention is particularly preferred to protect mammalian tissues and cells from oxidative stress. The cosmetic or dermatological preparations according to the invention serve especially the protection of human skin, hair and / or nails, against oxidative stress and the harmful influence of radicals.

The present invention also includes a method for protecting cosmetics shear, dermatological and food or pleasure accessories against oxidation or photo-oxidation, these accessories horse riding z. B. preparations for the treatment, protection and care of the skin, who can trade nails or hair or food and beverages, their components stability problems due to oxidation or photooxidation bring with it in storage, characterized in that according to the invention Preparations an effective content of 2-hydrazino-1,3-thi according to the invention have azoles.  

Examples

example 1

"Oil in water" emulsion

Part A was mixed and heated to 80 ° C. Part B was mixed and heated to 90 ° C heated and added to Part A with stirring. For part C, Carbopol was in water carefully dispersed and neutralized with sodium hydroxide solution (pH 6.9). Part C then became added at 60 ° C to the mixture of parts A and B. Part D became the Mi added from parts A, B, and C at room temperature.

Example 2

"Water in oil" sun protection emulsion with UVA / B broadband protection

For part A, all substances except the zinc oxide were heated to 85 ° C and that Zinc oxide carefully dispersed in the mixture. The components of part B was mixed, heated to 85 ° C and added to Part A with stirring. To the mix  from parts A and B part C was added and then Mi homogenized with a dispersing tool.

Example 3

"Oil in water" sun protection emulsion with UVA / B broadband protection

For Part A, all substances were mixed except for the titanium dioxide and to 85 ° C heated; the titanium dioxide was carefully dispersed into the mixture. For part B except Veegum and Natrosol, all substances were mixed, heated to 90 ° C, Dispersed Natrosol and Veegum and the mixture with stirring to part A ge give. Part C was added to the mixture of parts A and B and then finally homogenize the mixture with a dispersing tool.  

Example 4

"Oil in water" sun protection emulsion with UVA / B broadband protection

Part A was heated to 85 ° C. Carbopol and Keltrol were added to the rest of the Be dispersed cold constituents, the mixture heated to 85 ° C and added to part A. ben. Part C was immediately added to the mixture of parts A and B at 80 ° C ben and homogenized for 5 min with a dispersing tool. Part D was closed Lich added at room temperature and the mixture with a disperser homogenized stuff.

Example 5 Efficacy as a radical scavenger

The activity of the exemplary compounds as radical scavengers was compared with the compared to conventional radical scavengers. The DPPH- (1,1-diphenyl-2- Picryl-hydrazyl) test applied to remove radicals.

DPPH was dissolved in methanol to a concentration of 100 µmol / l. A number of dilutions of the exemplary compounds, vitamin C, α-tocopherol and dibutylhydroxytoluene were made in methanol. Methanol served as a control. 2500 μl of the DPPH solution were mixed with 500 μl of each test solution and the decrease in absorption at 515 nm was read until the decrease was less than 2% per hour. The activity of the test substances as radical scavengers was calculated according to the following equation:
Active, as radical scavenger (%) = 100 - (absorption of test compounds) / (absorption of control) × 100.

From the activity as radical scavenger (%) in a series of dilutions of test compounds, the effective relative concentration EC ₅₀ (based on the initially existing concentration of DPPH, EC = c (test compound) / c (DPPH)) became one for each test compound Test compound calculated with the radical DPPH removed by 50%. The results are shown in Table 1:

Table 1

Example 6 Activity as antioxidants

The activity of the exemplary compounds has been shown to be that of antioxidants compared to that of conventional antioxidants. The be accelerated autoxidation of lipids by air with or without antioxidant with Using the Rancimat apparatus applied (Rancimat is a registered Trademark of Metrohm AG, Herisau, Switzerland).  

The exemplary compounds, vitamin C, α-tocopherol and dibutylhydroxy toluene were dissolved in methanol or acetone and from the respective test solution Add 100 µl to a prepared 3 g oil sample. Was in a control sample only given solvents. By the heated oil containing the test solution A constant, dry air flow (20 l / h) was blown into the sample and the volatile Oxidation products (mainly short-chain fatty acids such as ants or vinegar acid) collected in a template with water. The conductivity of this watery Solution was continuously measured and documented. The oxidation of (unsung saturated) fats run very slowly for a while and then increase suddenly strong. The time to rise is called the induction period (IP) records.

The antioxidative index (AOI) was obtained according to the following equation:

AOI = IP _{(with test solution)} / IP _{(control sample)} .

The results for the experiments in soybean oil at 100 ° C and at 80 ° C in squalene, that was cleaned over alumina type N and stabilized with 1 ppm α-tocopherol, are shown in Table 2:  

Table 2

Claims (10)

1. Use of the 2-hydrazino-1,3-thiazoles of the general formula
or their salts,
in which
X represents a nitrogen atom or a substituted carbon atom CQ ² ,
and
either
Q ¹ and Q ² independently of one another are hydrogen atoms,
optionally hydroxyl- or alkyloxy-substituted unbranched, branched or cyclic alkyl, alkenyl, 1-oxoalkyl or 1-oxoalkenyl groups with 1 to 18 carbon atoms,
optionally substituted aryl groups with 6 to 15 carbon atoms,
optionally substituted heterocyclyl groups with 2 to 15 carbon atoms and at least one heteroatom selected from the group consisting of oxygen, nitrogen or sulfur,
optionally substituted arylalkyl or aryl-1-oxoalkyl groups of 7 to 16 carbon atoms,
Halogen atoms, nitro groups or
Represent groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁵ , -SO ₂ NR ⁴ R ⁵ or -PO (OR ⁴ ) (OR ⁵ ),
or
Q ¹ and Q ² together represent a radical of the general formula (II)
represent
in which
X ¹ , X ² and X ³ independently of one another represent either nitrogen atoms or carbon atoms with the radicals R ¹ , R ² or R ³ ,
and
R ¹ , R ² and R ³ independently of one another are hydrogen atoms,
optionally hydroxyl- or alkyloxy-substituted unbranched, branched or cyclic alkyl, alkenyl, 1-oxoalkyl or 1-oxo alkenyl groups with 1 to 18 carbon atoms,
optionally substituted aryl groups with 6 to 15 carbon atoms,
optionally substituted heterocyclyl groups with 2 to 15 carbon atoms and at least one heteroatom selected from the group consisting of oxygen, nitrogen or sulfur,
optionally substituted arylalkyl or aryl-1-oxoalkyl groups of 7 to 16 carbon atoms,
Halogen atoms, nitro groups or
Represent groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ NR ⁴ R ⁵ or -PO (OR ⁴ ) (OR ⁵ )
and
R ⁴ and R ⁵ independently of one another are hydrogen atoms, optionally hydroxyl- or alkyloxy-substituted unbranched, branched or cyclic alkyl, alkenyl, 1-oxoalkyl or 1-oxoalkenyl groups having 1 to 18 carbon atoms,
optionally substituted aryl groups with 6 to 15 carbon atoms,
optionally substituted arylalkyl or aryl-1-oxoalkyl groups of 7 to 16 carbon atoms,
represent
as antioxidants or radical scavengers. 2. Use of the 2-hydrazino-1,3-thiazoles of the general formula (I)
or their salts,
in which
X represents a nitrogen atom or a substituted carbon atom Q ² Q ² C-,
and
either
Q ¹ and Q ² independently of one another are hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl or acetyl groups, chlorine or fluorine atoms, nitro groups, Groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ NR ⁴ R ⁵ , -PO (OR ⁴ ) (OR ⁵ ), or on the aromatic optionally with alkyl, hydroxy , Alkyloxy, amino, dialkylamino, bromine, fluorine, chlorine, nitrile, sulfonic acid, sulfonamide or alkylsulfonate radicals represent substituted phenyl, pyridyl, pyrazinyl, phenylmethyl or benzoyl groups,
or
Q ¹ and Q ² together represent a radical of the general formula (II)
represent
in which
X ¹ , X ² and X ^{3 represent} carbon atoms with the radicals R ¹ , R ² and R ³ ,
and
R ¹ , R ² and R ³ independently of one another hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl or acetyl groups, phenyl, pyridyl -, Pyrazinyl groups, phenylmethyl, 4-methylphenylmethyl, 4-methoxyphenylmethyl or benzoyl groups, chlorine or fluorine atoms, nitro groups, groups -COOR ⁴ , -OR ⁴ , NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ Represent NR ⁴ R ⁵ or -PO (OR ⁴ ) (OR ⁵ )
and
R ⁴ and R ⁵ independently of one another are hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl, acetyl, propionyl or pivaloyl groups, phenyl groups Represent pyridyl, pyrazinyl, phenylmethyl, 4-methylphenylmethyl, 4-methoxyphenylmethyl or benzoyl groups
as antioxidants or radical scavengers. 3. Use of 2-hydrazino-1,3-benzothiazole, 5,6-dimethoxy-2-hydra zino-1,3-benzothiazole, 6-methoxy-2-hydrazino-1,3-benzothiazole, 2-hydra zino-1,3-benzothiazole-5-sulfonic acid, 2-hydrazino-1,3-benzothiazole-6- sulfonic acid, 6-tert-butyl-2-hydrazino-1,3-benzothiazole, 6-methyl-2-hydra zino-1,3-benzothiazole, 2-hydrazino-thiazolo- [5,4-b] pyridine, 2-hydrazino- 1,3-benzoxazole, 2-hydrazino-1H-benzimidazole, 2-hydrazino-5- (4-fluor phenyl) -1,3,4-thiadiazole, 2-hydrazino-4-phenyl-1,3-thiazole, 2-hydrazino-4- methyl-1,3-thiazole hydrochloride as an antioxidant or radical scavenger. 4. Cosmetic, dermatological and nutritional or pleasure-making preparations containing the 2-hydrazino-1,3-thiazoles of the general formula (I)
or their salts,
in which
X represents a nitrogen atom or a substituted carbon atom Q ² Q ² C-,
and
either
Q ¹ and Q ² independently of one another are hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl or acetyl groups, chlorine or fluorine atoms, nitro groups, Groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ NR ⁴ R ⁵ , -PO (OR ⁴ ) (OR ⁵ ), or on the aromatic optionally with alkyl, hydroxy , Alkyloxy, amino, dialkylamino, bromine, fluorine, chlorine, nitrile, sulfonic acid, sulfonamide or alkylsulfonate radicals represent substituted phenyl, pyridyl, pyrazinyl, phenylmethyl or benzoyl groups,
or
Q ¹ and Q ² together represent a radical of the general formula (II)
represent
in which
X ¹ , X ² and X ^{3 represent} carbon atoms with the radicals R ¹ , R ² and R ³ ,
and
R ¹ , R ² and R ³ independently of one another hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl or acetyl groups, phenyl, pyridyl -, Pyrazinyl groups, phenylmethyl, 4-methylphenylmethyl, 4-methoxyphenylmethyl or benzoyl groups, chlorine or fluorine atoms, nitro groups, groups -COOR ⁴ , -OR ⁴ , -NR ⁴ R ⁵ , -SO ₂ OR ⁴ , -SO ₂ NR ⁴ R ⁵ or -PO (OR ⁴ ) (OR ⁵ )
and
R ⁴ and R ⁵ independently of one another are hydrogen atoms, methyl, trifluoromethyl, ethyl, tert-butyl, allyl, 3-methylbut-2-en-1-yl, acetyl, propionyl or pivaloyl groups, phenyl groups Represent pyridyl, pyrazinyl, phenylmethyl, 4-methylphenylmethyl, 4-methoxyphenylmethyl or benzoyl groups. 5. Cosmetic and dermatological preparations containing 0.0001% by weight up to 30% by weight, preferably 0.001 to 20% by weight, particularly preferably 0.01 to 5 wt .-% of the 2-hydrazino-1,3-thiazoles according to claims 1 to 3, based on the total weight of the preparations. 6. Nutritional or pleasure-making preparations containing 0.0001% by weight to 30% by weight, preferably 0.001 to 20% by weight, in particular preferably 0.01 to 5 wt .-% of the 2-hydrazino-1,3-thiazoles according to the An sayings 1 to 3, based on the total weight of the preparations. 7. Use of the preparations according to claims 4 to 6 as antioxidants dantien and / or radical scavenger. 8. Preparations according to claim 4, which additionally have at least one UVA and / or contain UVB filter substance.   9. Preparations according to claims 4 to 6, which additionally at least one contain another antioxidant or a radical scavenger. 10. Preparations according to claims 4 to 6, which additionally at least one UVA and / or UVB filter substance and at least one other antioxidant or contain a radical scavenger.